72 CLINICAL REPORTS Polyglandular autoimmune syndrome type III associated with coeliac disease and sarcoidosis Konstantin I. Papadopoulos and Bengt Hallengren Department of Endocrinology, Lund University Clinics, General Hospital, S-21401 Malmi, Sweden Summary: A female patient demonstrating a previously not reported constellation of polyglandular autoimmune syndrome type III (including autoimmune thyroiditis, Graves' ophthalmopathy, insulin- dependent diabetes mellitus and vitiligo), coeliac disease and sarcoidosis is described. This may be a random association but might also indicate a common immunological and/or genetic disturbance. Introduction Autoimmune disorders and sarcoidosis may be related' and the association between sarcoidosis and autoimmune thyroid disease has long been recognized.2'3 Polyglandular autoimmune (PGA) syndromes4 occurring together with sarcoidosis have only been described in a few cases.2517 How- ever, none of these was associated with coeliac disease. We would like to report a female patient with PGA syndrome type III (autoimmune thyroid disease, insulin-dependent diabetes mellitus (IDDM), vitiligo), coeliac disease, transiently positive adrenal antibodies and sarcoidosis. Methods Serum microsomal antibodies and thyroglobulin antibodies were measured by complement binding reaction and passive haemagglutination, respec- tively. Serum adrenal, gluten (IgA/IgG), reticulin, parietal cell, smooth muscle, glomerular and mitochondrial antibodies as well as antinuclear factors were measured by immunofluorescence. The HLA haplotype was analysed in Lund's trans- plantation laboratory according to the method of Vartdal et al.8 Case report A female patient born in 1941, without known heredity for autoimmune diseases, was admitted in 1970 to our department due to polyuria, polydipsia and weight loss and IDDM was diagnosed. In 1976 a nodular goitre was noted, thyrotrophin was 8 mIU/I (reference range <8), serum antibodies against microsomal antigen (titre 1/640, reference value < 1/10) and thyroglobulin antibodies (titre 1/10, reference value < 1/10) were present and L-thyroxine was instituted. In October 1984 the patient complained of gritty foreign body sensation in the eyes associated with redness, tearing and photophobia. On examina- tion, lid retraction, periorbital oedema, conjunc- tival injection and slight chemosis were noted. Exophthalmometry ad modum Krahn demon- strated readings of 12 mm in the right and 14 mm in the left eye. Eye movements and a computerized tomographic (CT) scan of the orbits were normal. The patient was euthyroid and thyroid-stimulating immunoglobulins were not demonstrated in the serum. Fine needle biopsy of the thyroid revealed autoimmune thyroiditis. The clinical diagnosis was Graves' ophthalmopathy. In April 1985 the patient complained of epigas- tric discomfort and frequent diarrhoea. Anaemia (erythrocyte sedimentation rate 35 mm/hour) with sideropenia and low blood folate 18 nmol/l (reference range 70-200) but a normal bone mar- row aspiration were noted. An electrophoresis of the plasma proteins showed a polyclonal rise of IgA 4.6 g/l (reference range 0.5-3.0) and a low serum albumin 33 g/l (reference range 36-48). Serum antibodies against adrenal antigen (titre 1/20, reference value < 1/10), gluten (IgA/IgG: 9.0/ 5.3 U/ml, reference value: 2.5/3.0 U/ml) and reticulin (titre 1/100, reference value < 1/10) were demonstrated. Hepatitis B surface antigen and serum antibodies against cytomegalovirus, parietal cell, smooth muscle, glomeruli and mitochondriae as well as antinuclear factor were not detected. Islet cell antibodies were not analysed. A morning serum ACTH, a morning serum cortisol and a short synthetic ACTH stimulation test were nor- mal. A computed tomographic (CT) scan of the abdomen including the adrenals was normal. A Correspondence: Bengt Hallengren, M.D., Ph.D. Accepted: 10 July 1992 copyright. on February 12, 2023 by guest. Protected by http://pmj.bmj.com/ Postgrad Med J: first published as 10.1136/pgmj.69.807.72 on 1 January 1993. Downloaded from
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Polyglandular autoimmune syndrome type III associated with coeliac disease and sarcoidosis
Konstantin I. Papadopoulos and Bengt Hallengren
Department ofEndocrinology, Lund University Clinics, General Hospital, S-21401 Malmi, Sweden
Summary: A female patient demonstrating a previously not reported constellation of polyglandular autoimmune syndrome type III (including autoimmune thyroiditis, Graves' ophthalmopathy, insulin- dependent diabetes mellitus and vitiligo), coeliac disease and sarcoidosis is described. This may be a random association but might also indicate a common immunological and/or genetic disturbance.
Introduction
Autoimmune disorders and sarcoidosis may be related' and the association between sarcoidosis and autoimmune thyroid disease has long been recognized.2'3 Polyglandular autoimmune (PGA) syndromes4 occurring together with sarcoidosis have only been described in a few cases.2517 How- ever, none of these was associated with coeliac disease. We would like to report a female patient with PGA syndrome type III (autoimmune thyroid disease, insulin-dependent diabetes mellitus (IDDM), vitiligo), coeliac disease, transiently positive adrenal antibodies and sarcoidosis.
Methods
Serum microsomal antibodies and thyroglobulin antibodies were measured by complement binding reaction and passive haemagglutination, respec- tively. Serum adrenal, gluten (IgA/IgG), reticulin, parietal cell, smooth muscle, glomerular and mitochondrial antibodies as well as antinuclear factors were measured by immunofluorescence. The HLA haplotype was analysed in Lund's trans- plantation laboratory according to the method of Vartdal et al.8
Case report
A female patient born in 1941, without known heredity for autoimmune diseases, was admitted in 1970 to our department due to polyuria, polydipsia and weight loss and IDDM was diagnosed. In 1976 a nodular goitre was noted, thyrotrophin was 8 mIU/I (reference range <8), serum antibodies
against microsomal antigen (titre 1/640, reference value < 1/10) and thyroglobulin antibodies (titre 1/10, reference value < 1/10) were present and L-thyroxine was instituted.
In October 1984 the patient complained of gritty foreign body sensation in the eyes associated with redness, tearing and photophobia. On examina- tion, lid retraction, periorbital oedema, conjunc- tival injection and slight chemosis were noted. Exophthalmometry ad modum Krahn demon- strated readings of 12 mm in the right and 14 mm in the left eye. Eye movements and a computerized tomographic (CT) scan of the orbits were normal. The patient was euthyroid and thyroid-stimulating immunoglobulins were not demonstrated in the serum. Fine needle biopsy of the thyroid revealed autoimmune thyroiditis. The clinical diagnosis was Graves' ophthalmopathy.
In April 1985 the patient complained of epigas- tric discomfort and frequent diarrhoea. Anaemia (erythrocyte sedimentation rate 35 mm/hour) with sideropenia and low blood folate 18 nmol/l (reference range 70-200) but a normal bone mar- row aspiration were noted. An electrophoresis of the plasma proteins showed a polyclonal rise ofIgA 4.6 g/l (reference range 0.5-3.0) and a low serum albumin 33 g/l (reference range 36-48). Serum antibodies against adrenal antigen (titre 1/20, reference value < 1/10), gluten (IgA/IgG: 9.0/ 5.3 U/ml, reference value: 2.5/3.0 U/ml) and reticulin (titre 1/100, reference value < 1/10) were demonstrated. Hepatitis B surface antigen and serum antibodies against cytomegalovirus, parietal cell, smooth muscle, glomeruli and mitochondriae as well as antinuclear factor were not detected. Islet cell antibodies were not analysed. A morning serum ACTH, a morning serum cortisol and a short synthetic ACTH stimulation test were nor- mal. A computed tomographic (CT) scan of the abdomen including the adrenals was normal. A
Correspondence: Bengt Hallengren, M.D., Ph.D. Accepted: 10 July 1992
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chest X-ray examination demonstrated bilateral hilar lymphadenopathy but no parenchymal involvement. A mediastinal lymph node biopsy showed multiple non-caseating giant epitheloid cell granulomas compatible with sarcoidosis (Figure 1) and without evidence of malignant disease. Stain- ing for mycobacteria and fungi was negative, as was culture of the biopsy specimen. Culture and direct microscopy of sputum and of specimens obtained by gastric lavage were negative for mycobacteria. Pulmonary function tests and arterial blood gases were normal. A Mantoux test was negative. A small bowel biopsy by Crosby capsule revealed total villous atrophy without sarcoid granulomas and was compatible with coeliac disease (Figure 2). The patient was dis- charged on a gluten-free diet and her condition improved markedly.
In July 1986 patchy vitiligo was observed. Nor- mal visual acuity but deteriorating ophthalmo- pathy with protrusion (17 mm on the right, 16 mm on the left eye) and diplopia with restricted eye movements was noted. A CT scan disclosed enlargement of extraocular muscles. Oral cortico- steroids were administered (prednisolone 30 mg/ day) but were ineffective and in November 1986 the patient was given retrobulbar irradiation (30 Gy). The ophthalmopathy improved and cor- ticosteroids could be finally withdrawn in May
1988. In March 1988 a chest radiograph and a new small bowel biopsy were normal. In November 1986 and in July 1990 no adrenal antibodies could be detected in the serum and a synthetic ACTH stimulation test was again normal. The HLA haplotype was A1,3; B8,40; Cw3,w7; DR3,6; DQ1,2.
Discussion
This patient had PGA syndrome type III defined as autoimmune thyroid disease occurring together with IDDM and/or pernicious anaemia and/or vitiligo/alopecia.4 In the present case, autoimmune thyroiditis, Graves' ophthalmopathy, IDDM and vitiligo were concurrent, and to the best of our knowledge this is the first report of a patient with PGA syndrome type III, coeliac disease and sar- coidosis. In addition, transiently positive adrenal antibodies in serum were detected indicating that our patient might develop Addison's disease and thus fulfil the criteria for PGA syndrome type II defined as Addison's disease and autoimmune thyroid disease and/or IDDM.4 Whether there was a causal relationship between the treatment with corticosteroids and the disappearance of the adrenal antibodies is open to speculation. Although the association between sarcoidosis
4t( *~~~~~~
f
Figure 1 Mediastinal lymph node biopsy showing non-caseating giant epitheloid cell granulomas compatible with sarcoidosis (haematoxylin and eosin, x 125).
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Figure 2 Small bowel biopsy showing total villous atrophy without sarcoid granulomas compatible with coeliac disease (haematoxylin and eosin, x 125).
and autoimmune thyroid disease has long been recognized2'3 the association of sarcoidosis with PGA syndromes has been reported in only a few cases almost exclusively with the PGA syndrome type II,'-' except in one report describing Graves' thyrotoxicosis, pernicious anaemia and vitiligo (PGA syndrome type III) in a patient with sar- coidosis.2 However, coeliac disease was not noted in any of the aforementioned cases. IDDM was diagnosed before thyroiditis in our patient, a pattern previously observed in PGA syndromes.9"lo
Coeliac disease, also regarded as an autoimmune disease," has been described in association with the PGA syndrome type III.' Coeliac disease and sarcoidosis occurring together in the same patient has recently been described in five cases'2 and in addition a high frequency of antibodies against gliadin (41%) was found in a recent study of patients with sarcoidosis, where one of the patients with gliadin antibodies showed total villous atrophy consistent with coeliac disease.' Although the pathogenesis of sarcoidosis is
unknown, it is probably a disease promoted by aberrations in immunological reactivity'4 and a combination of abnormalities of some aspects ofT cell function with enhanced or normal ability of B cells to produce antibodies'4 has been documented.
The pathogenesis of autoimmune endocrine diseases involves a HLA-linked genetic suscepti- bility and a probable environment-induced ini- tiating event, leading to an abnormal immune response in which both humoral and cellular mechanisms are involved.'5 The HLA haplotype of our patient (A 1,3; B8,40; Cw3,w7; DR3,6; DQ1,2) was in good accordance with the findings of HLA Al, B8, DR3, Dw3, DR4 being more frequent in patients with the PGA syndromes type II and III,4 with adult coeliac disease4 or with sarcoidosis,'6 as compared to the general population. This indicates a common underlying genetic predisposition for these conditions.4
In conclusion, the patient described demon- strates a previously unreported constellation of PGA syndrome type III, coeliac disease and sar- coidosis, which may be a random association but might also indicate a common immunological and/or genetic disturbance.
Acknowledgement
We wish to thank Associate Professor L. Bondesson for evaluating the histological tissue preparations and Dr J. Kurkus for the HLA analysis.
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References
1. Wiesenbutter, C.W. & Sharma, O.P. Is sarcoidosis an auto- immune disorder? Report of four cases and review of literature. Semin Arthritis Rhewn 1979, 9 124-144.
2. Hanock, B.W. & Millard, L.G. Sarcoidosis and thyro- toxicosis. A study of five patients. Br J Dis Chest 1976, 70: 129- 133.
3. Bell, N.H. Endocrine complications of sarcoidosis. Endo- crinol Metab Clin North Am 1991, 20: 645-654.
4. Neufeld, M., Maclaren, N.K. & Blizzard, R. Autoimmune polyglandular syndromes. Pediatr Ann 1980, 9: 154-163.
5. Karlish, A.J. & MacGregor, G.A. Sarcoidosis, thyroiditis and Addison's disease. Lancet 1970, ii: 330-333.
6. Seinfield, E.D. & Sharma, O.P. TASS syndrome: unusual association of thyroiditis, Addison's disease, Sjogren syn- drome and sarcoidosis. J R Soc Med 1983, 76: 883-885.
7. Waltz, B. From GLA: Addison's disease and sarcoidosis: unusual frequency of coexisting hypothyroidism (Schmidt's syndrome) (letter). Am J Med 1990, 89: 692-693.
8. Vartdal, F., Gaudernack, G., Funderud, S. et al. HLA Class I and II typing using cells positively selected from blood by immunomagnetic isolation - a fast and reliable technique. Tissue Antigens 1986, 28: 301-312.
9. Gray, R.S., Herd, R. & Clarke, B.F. The clinical features of diabetes with coexisting autoimmune disease. Diabetol 1981, 20: 602-606.
10. Papadopoulos, K.I. & Hallengren, B. Polyglandular auto- immune syndrome type II in patients with idiopathic Addison's disease. Acta Endocrinol (Copenh) 1990, 122: 472-478.
11. Ferguson, A., Macdonald, T.T., McClure, J.P. & Holden, R.J. Cell-mediated immunity to gliadin within the small intestinal mucosa in coeliac disease. Lancet 1975, i: 895-897.
12. Douglas, J.G., Gillon, J., Logan, R.F.A., Grant, I.W.B. & Cromton, G.K. Sarcoidosis and coeliac disease: an associa- tion? Lancet 1984, ui: 13-15.
13. McCormick, P.A., Feighery, C., Dolan, C. et al. Altered gastrointestinal immune response in sarcoidosis. Gut 1988, 29: 1628-1631.
14. Poulter, L.W. Immune aspects ofsarcoidosis. PostgradMedJ 1988, 64: 536-543.
15. Holland, F.J., McConnon, J.K., Volpe, R. & Saunders, E.F. Concordant Graves' disease after bone marrow transplanta- tion: implications for pathogenesis. J Clin Endocrinol Metab 1991, 72: 837-840.
16. Hedfors, E. & Linstrom, F. HLA - B8/DR3 in sarcoidosis. Tissue Antigens 1983, 22: 200-203.
Obstructive uropathy due to extramedullary haemato- poiesis in beta thalassaemia/haemoglobin E
Tanin Intragumtornchai, Kiat Arjhansiri', Makumkrong Posayachindal and Vira Kasantikul2
Departments ofMedicine, 'Radiology and 2Pathology, Faculty ofMedicine, Chulalongkorn University, Bangkok 10330, Thailand
Summary: An 18 year old woman with beta thalassaemia/haemoglobin E developed a large pelvic tumour resulting in bilateral obstructive uropathy. Technetium-99m sulphur colloid marrow image, computed tomographic scan of the abdomen and needle biopsy of the mass confirmed the diagnosis of extramedullary haematopoiesis. Although radiation is the treatment of choice for decompression, the mass in this patient did not respond satisfactorily due to its multiple area of tumour autoinfarction. Obstructive uropathy due to extramedullary erythropoiesis has not to our knowledge been previously described.
Introduction
Extramedullary haematopoiesis, a common mani- festation of severe thalassaemia, occurs as a conse- quence of uninhibited erythropoiesis.' Common sites of involvement include the posterior medias- tinum, liver and spleen. Generally these extramed- ullary haematopoietic masses are asymptomatic, although spinal cord compression has been fre-
quently cited.2'3 A patient with beta thalassaemia/ haemoglobin E in whom an unusually large pelvic extramedullary haematopoietic mass resulted in severe bilateral obstructive uropathy prompts this report.
Case report
An 18 year old woman with the diagnosis of beta thalassaemia/haemoglobin E since the age of 10
Correspondence: Tanin Intragumtornchai, M.D. Accepted: 18 June 1992
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ed J: first published as 10.1136/pgm j.69.807.72 on 1 January 1993. D
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Konstantin I. Papadopoulos and Bengt Hallengren
Department ofEndocrinology, Lund University Clinics, General Hospital, S-21401 Malmi, Sweden
Summary: A female patient demonstrating a previously not reported constellation of polyglandular autoimmune syndrome type III (including autoimmune thyroiditis, Graves' ophthalmopathy, insulin- dependent diabetes mellitus and vitiligo), coeliac disease and sarcoidosis is described. This may be a random association but might also indicate a common immunological and/or genetic disturbance.
Introduction
Autoimmune disorders and sarcoidosis may be related' and the association between sarcoidosis and autoimmune thyroid disease has long been recognized.2'3 Polyglandular autoimmune (PGA) syndromes4 occurring together with sarcoidosis have only been described in a few cases.2517 How- ever, none of these was associated with coeliac disease. We would like to report a female patient with PGA syndrome type III (autoimmune thyroid disease, insulin-dependent diabetes mellitus (IDDM), vitiligo), coeliac disease, transiently positive adrenal antibodies and sarcoidosis.
Methods
Serum microsomal antibodies and thyroglobulin antibodies were measured by complement binding reaction and passive haemagglutination, respec- tively. Serum adrenal, gluten (IgA/IgG), reticulin, parietal cell, smooth muscle, glomerular and mitochondrial antibodies as well as antinuclear factors were measured by immunofluorescence. The HLA haplotype was analysed in Lund's trans- plantation laboratory according to the method of Vartdal et al.8
Case report
A female patient born in 1941, without known heredity for autoimmune diseases, was admitted in 1970 to our department due to polyuria, polydipsia and weight loss and IDDM was diagnosed. In 1976 a nodular goitre was noted, thyrotrophin was 8 mIU/I (reference range <8), serum antibodies
against microsomal antigen (titre 1/640, reference value < 1/10) and thyroglobulin antibodies (titre 1/10, reference value < 1/10) were present and L-thyroxine was instituted.
In October 1984 the patient complained of gritty foreign body sensation in the eyes associated with redness, tearing and photophobia. On examina- tion, lid retraction, periorbital oedema, conjunc- tival injection and slight chemosis were noted. Exophthalmometry ad modum Krahn demon- strated readings of 12 mm in the right and 14 mm in the left eye. Eye movements and a computerized tomographic (CT) scan of the orbits were normal. The patient was euthyroid and thyroid-stimulating immunoglobulins were not demonstrated in the serum. Fine needle biopsy of the thyroid revealed autoimmune thyroiditis. The clinical diagnosis was Graves' ophthalmopathy.
In April 1985 the patient complained of epigas- tric discomfort and frequent diarrhoea. Anaemia (erythrocyte sedimentation rate 35 mm/hour) with sideropenia and low blood folate 18 nmol/l (reference range 70-200) but a normal bone mar- row aspiration were noted. An electrophoresis of the plasma proteins showed a polyclonal rise ofIgA 4.6 g/l (reference range 0.5-3.0) and a low serum albumin 33 g/l (reference range 36-48). Serum antibodies against adrenal antigen (titre 1/20, reference value < 1/10), gluten (IgA/IgG: 9.0/ 5.3 U/ml, reference value: 2.5/3.0 U/ml) and reticulin (titre 1/100, reference value < 1/10) were demonstrated. Hepatitis B surface antigen and serum antibodies against cytomegalovirus, parietal cell, smooth muscle, glomeruli and mitochondriae as well as antinuclear factor were not detected. Islet cell antibodies were not analysed. A morning serum ACTH, a morning serum cortisol and a short synthetic ACTH stimulation test were nor- mal. A computed tomographic (CT) scan of the abdomen including the adrenals was normal. A
Correspondence: Bengt Hallengren, M.D., Ph.D. Accepted: 10 July 1992
copyright. on F
http://pm j.bm
P ostgrad M
ed J: first published as 10.1136/pgm j.69.807.72 on 1 January 1993. D
ow nloaded from
chest X-ray examination demonstrated bilateral hilar lymphadenopathy but no parenchymal involvement. A mediastinal lymph node biopsy showed multiple non-caseating giant epitheloid cell granulomas compatible with sarcoidosis (Figure 1) and without evidence of malignant disease. Stain- ing for mycobacteria and fungi was negative, as was culture of the biopsy specimen. Culture and direct microscopy of sputum and of specimens obtained by gastric lavage were negative for mycobacteria. Pulmonary function tests and arterial blood gases were normal. A Mantoux test was negative. A small bowel biopsy by Crosby capsule revealed total villous atrophy without sarcoid granulomas and was compatible with coeliac disease (Figure 2). The patient was dis- charged on a gluten-free diet and her condition improved markedly.
In July 1986 patchy vitiligo was observed. Nor- mal visual acuity but deteriorating ophthalmo- pathy with protrusion (17 mm on the right, 16 mm on the left eye) and diplopia with restricted eye movements was noted. A CT scan disclosed enlargement of extraocular muscles. Oral cortico- steroids were administered (prednisolone 30 mg/ day) but were ineffective and in November 1986 the patient was given retrobulbar irradiation (30 Gy). The ophthalmopathy improved and cor- ticosteroids could be finally withdrawn in May
1988. In March 1988 a chest radiograph and a new small bowel biopsy were normal. In November 1986 and in July 1990 no adrenal antibodies could be detected in the serum and a synthetic ACTH stimulation test was again normal. The HLA haplotype was A1,3; B8,40; Cw3,w7; DR3,6; DQ1,2.
Discussion
This patient had PGA syndrome type III defined as autoimmune thyroid disease occurring together with IDDM and/or pernicious anaemia and/or vitiligo/alopecia.4 In the present case, autoimmune thyroiditis, Graves' ophthalmopathy, IDDM and vitiligo were concurrent, and to the best of our knowledge this is the first report of a patient with PGA syndrome type III, coeliac disease and sar- coidosis. In addition, transiently positive adrenal antibodies in serum were detected indicating that our patient might develop Addison's disease and thus fulfil the criteria for PGA syndrome type II defined as Addison's disease and autoimmune thyroid disease and/or IDDM.4 Whether there was a causal relationship between the treatment with corticosteroids and the disappearance of the adrenal antibodies is open to speculation. Although the association between sarcoidosis
4t( *~~~~~~
f
Figure 1 Mediastinal lymph node biopsy showing non-caseating giant epitheloid cell granulomas compatible with sarcoidosis (haematoxylin and eosin, x 125).
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P ostgrad M
ed J: first published as 10.1136/pgm j.69.807.72 on 1 January 1993. D
ow nloaded from
Figure 2 Small bowel biopsy showing total villous atrophy without sarcoid granulomas compatible with coeliac disease (haematoxylin and eosin, x 125).
and autoimmune thyroid disease has long been recognized2'3 the association of sarcoidosis with PGA syndromes has been reported in only a few cases almost exclusively with the PGA syndrome type II,'-' except in one report describing Graves' thyrotoxicosis, pernicious anaemia and vitiligo (PGA syndrome type III) in a patient with sar- coidosis.2 However, coeliac disease was not noted in any of the aforementioned cases. IDDM was diagnosed before thyroiditis in our patient, a pattern previously observed in PGA syndromes.9"lo
Coeliac disease, also regarded as an autoimmune disease," has been described in association with the PGA syndrome type III.' Coeliac disease and sarcoidosis occurring together in the same patient has recently been described in five cases'2 and in addition a high frequency of antibodies against gliadin (41%) was found in a recent study of patients with sarcoidosis, where one of the patients with gliadin antibodies showed total villous atrophy consistent with coeliac disease.' Although the pathogenesis of sarcoidosis is
unknown, it is probably a disease promoted by aberrations in immunological reactivity'4 and a combination of abnormalities of some aspects ofT cell function with enhanced or normal ability of B cells to produce antibodies'4 has been documented.
The pathogenesis of autoimmune endocrine diseases involves a HLA-linked genetic suscepti- bility and a probable environment-induced ini- tiating event, leading to an abnormal immune response in which both humoral and cellular mechanisms are involved.'5 The HLA haplotype of our patient (A 1,3; B8,40; Cw3,w7; DR3,6; DQ1,2) was in good accordance with the findings of HLA Al, B8, DR3, Dw3, DR4 being more frequent in patients with the PGA syndromes type II and III,4 with adult coeliac disease4 or with sarcoidosis,'6 as compared to the general population. This indicates a common underlying genetic predisposition for these conditions.4
In conclusion, the patient described demon- strates a previously unreported constellation of PGA syndrome type III, coeliac disease and sar- coidosis, which may be a random association but might also indicate a common immunological and/or genetic disturbance.
Acknowledgement
We wish to thank Associate Professor L. Bondesson for evaluating the histological tissue preparations and Dr J. Kurkus for the HLA analysis.
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http://pm j.bm
P ostgrad M
ed J: first published as 10.1136/pgm j.69.807.72 on 1 January 1993. D
ow nloaded from
References
1. Wiesenbutter, C.W. & Sharma, O.P. Is sarcoidosis an auto- immune disorder? Report of four cases and review of literature. Semin Arthritis Rhewn 1979, 9 124-144.
2. Hanock, B.W. & Millard, L.G. Sarcoidosis and thyro- toxicosis. A study of five patients. Br J Dis Chest 1976, 70: 129- 133.
3. Bell, N.H. Endocrine complications of sarcoidosis. Endo- crinol Metab Clin North Am 1991, 20: 645-654.
4. Neufeld, M., Maclaren, N.K. & Blizzard, R. Autoimmune polyglandular syndromes. Pediatr Ann 1980, 9: 154-163.
5. Karlish, A.J. & MacGregor, G.A. Sarcoidosis, thyroiditis and Addison's disease. Lancet 1970, ii: 330-333.
6. Seinfield, E.D. & Sharma, O.P. TASS syndrome: unusual association of thyroiditis, Addison's disease, Sjogren syn- drome and sarcoidosis. J R Soc Med 1983, 76: 883-885.
7. Waltz, B. From GLA: Addison's disease and sarcoidosis: unusual frequency of coexisting hypothyroidism (Schmidt's syndrome) (letter). Am J Med 1990, 89: 692-693.
8. Vartdal, F., Gaudernack, G., Funderud, S. et al. HLA Class I and II typing using cells positively selected from blood by immunomagnetic isolation - a fast and reliable technique. Tissue Antigens 1986, 28: 301-312.
9. Gray, R.S., Herd, R. & Clarke, B.F. The clinical features of diabetes with coexisting autoimmune disease. Diabetol 1981, 20: 602-606.
10. Papadopoulos, K.I. & Hallengren, B. Polyglandular auto- immune syndrome type II in patients with idiopathic Addison's disease. Acta Endocrinol (Copenh) 1990, 122: 472-478.
11. Ferguson, A., Macdonald, T.T., McClure, J.P. & Holden, R.J. Cell-mediated immunity to gliadin within the small intestinal mucosa in coeliac disease. Lancet 1975, i: 895-897.
12. Douglas, J.G., Gillon, J., Logan, R.F.A., Grant, I.W.B. & Cromton, G.K. Sarcoidosis and coeliac disease: an associa- tion? Lancet 1984, ui: 13-15.
13. McCormick, P.A., Feighery, C., Dolan, C. et al. Altered gastrointestinal immune response in sarcoidosis. Gut 1988, 29: 1628-1631.
14. Poulter, L.W. Immune aspects ofsarcoidosis. PostgradMedJ 1988, 64: 536-543.
15. Holland, F.J., McConnon, J.K., Volpe, R. & Saunders, E.F. Concordant Graves' disease after bone marrow transplanta- tion: implications for pathogenesis. J Clin Endocrinol Metab 1991, 72: 837-840.
16. Hedfors, E. & Linstrom, F. HLA - B8/DR3 in sarcoidosis. Tissue Antigens 1983, 22: 200-203.
Obstructive uropathy due to extramedullary haemato- poiesis in beta thalassaemia/haemoglobin E
Tanin Intragumtornchai, Kiat Arjhansiri', Makumkrong Posayachindal and Vira Kasantikul2
Departments ofMedicine, 'Radiology and 2Pathology, Faculty ofMedicine, Chulalongkorn University, Bangkok 10330, Thailand
Summary: An 18 year old woman with beta thalassaemia/haemoglobin E developed a large pelvic tumour resulting in bilateral obstructive uropathy. Technetium-99m sulphur colloid marrow image, computed tomographic scan of the abdomen and needle biopsy of the mass confirmed the diagnosis of extramedullary haematopoiesis. Although radiation is the treatment of choice for decompression, the mass in this patient did not respond satisfactorily due to its multiple area of tumour autoinfarction. Obstructive uropathy due to extramedullary erythropoiesis has not to our knowledge been previously described.
Introduction
Extramedullary haematopoiesis, a common mani- festation of severe thalassaemia, occurs as a conse- quence of uninhibited erythropoiesis.' Common sites of involvement include the posterior medias- tinum, liver and spleen. Generally these extramed- ullary haematopoietic masses are asymptomatic, although spinal cord compression has been fre-
quently cited.2'3 A patient with beta thalassaemia/ haemoglobin E in whom an unusually large pelvic extramedullary haematopoietic mass resulted in severe bilateral obstructive uropathy prompts this report.
Case report
An 18 year old woman with the diagnosis of beta thalassaemia/haemoglobin E since the age of 10
Correspondence: Tanin Intragumtornchai, M.D. Accepted: 18 June 1992
copyright. on F
http://pm j.bm
P ostgrad M
ed J: first published as 10.1136/pgm j.69.807.72 on 1 January 1993. D
ow nloaded from
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